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Peptides derived from cadherin juxtamembrane region inhibit platelet function.

ABSTRACT: The juxtamembrane domains (JMD) of transmembrane proteins are rich in critical peptide sequences that participate in dynamic cell signalling events. Synthetic JMD peptides derived from cadherin cell adhesion proteins have previously been shown to modulate platelet function. In this study, we aimed to develop functional bioactive agents from bioinformatically identified critical peptide sequences. We synthesized overlapping 12-15 amino acid peptides from E- and N-cadherin JMD and assessed their effect on platelet aggregation and platelet ATP secretion. Peptides derived from close to the membrane proximal region inhibit platelet function. Sequential deletion of amino acids from the N- and C-termini of the inhibitory E-cadherin peptides identified the short K756EPLLP763 motif as a critical bioactive sequence. Alanine scanning studies further identified that the di-leucine (LL) motif and positively charged lysine (K) are crucial for peptide activity. Moreover, scrambled peptides failed to show any effect on platelet activity. We conclude that peptides derived from JMD of E-cadherin provide potential lead peptides for the development of anti-thrombotic agents and to enable further understanding of the role of cadherins in platelet function.

SUBMITTER: Golla K

PROVIDER: S-EPMC6227957 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Peptides derived from cadherin juxtamembrane region inhibit platelet function.

Golla Kalyan K Stavropoulos Ilias I Shields Denis C DC Moran Niamh N

Royal Society open science 20181010 10

The juxtamembrane domains (JMD) of transmembrane proteins are rich in critical peptide sequences that participate in dynamic cell signalling events. Synthetic JMD peptides derived from cadherin cell adhesion proteins have previously been shown to modulate platelet function. In this study, we aimed to develop functional bioactive agents from bioinformatically identified critical peptide sequences. We synthesized overlapping 12-15 amino acid peptides from E- and N-cadherin JMD and assessed their e ...[more]

PMID: 30473799

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Dataset Information

Peptides derived from cadherin juxtamembrane region inhibit platelet function.

Publications

Peptides derived from cadherin juxtamembrane region inhibit platelet function.

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